Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Mullerian inhibiting substance (MIS) is a member of the transforming growth factor-β (TGFβ) superfamily of secreted protein hormones that signal through receptor complexes of type I and type II serine/threonine kinase receptors. The binding of MIS ligand to its receptor initiates a signaling cascade, including phosphorylation of Smad1, that is dependent on recruitment of type I receptors, ALK2 and ALK6, which also signal for bone morphogenetic proteins (Segev et al. (2001) J. Biol. Chem., 276:26799-26806). MIS type II receptor (MISIIR) has been detected on human gynecological cancers (e.g., cervical, ovarian, uterine, vaginal, and vulvar), prostate cancers, and breast cancers (e.g., ductal carcinomas; Segev et al. (2000) J. Biol. Chem., 275:28371-28379; Segev et al. (2001) J. Biol. Chem., 276:26799-26806; Segev et al. (2002) Proc. Natl. Acad. Sci., 99:239-244; Barbie et al. (2003) Proc. Natl. Acad. Sci., 100:15601-15606; Masiakos et al. (1999) Clin. Cancer Res., 5:3488-99; Hoshiya (2003) J. Biol. Chem., 278:51703-12; Hoshiya et al. (2003) Mol. Cell. Endocrinol., 211:43-9; Yuan et al. (2006) Mol. Cancer Ther., 5:2096-105; Song et al. (2009) Int. J. Oncol., 34:1583-91; Bakkum-Gamez et al. (2008) Gynecol. Oncol., 108:141-8). Additionally, the expression of the Simian Virus 40 TAg under Control of the MISIIR Promoter was found to lead to the generation of testicular tumors in transgenic mice, suggesting a role in testicular cancer (Connolly et al. (2003) Cancer Res., 63:1389-97). These findings demonstrate the relevance of MISIIR for anti-cancer therapies.